目的 研究土鳖虫活性肽LL8在正常大鼠体内的药动学，并考察LL8对高脂血症大鼠模型的影响。方法 采用异硫氰酸荧光素（fluorescein isothiocyanate，FITC）对LL8进行N端标记（FITC-LL8），SD大鼠随机分为FITC-LL8高、低剂量（10、5 mg/kg）组，各给药组im相应药物，于不同时间点眼眶取血，采用EnSpire多标记微孔板检测酶标仪，辅以DAS 2.0药动学数据处理软件，以偏最小二乘法为计算原则，根据药动学理论得出FITC-LL8在SD大鼠体内的药动学变化。SD大鼠随机分为对照组、模型组、辛伐他汀（200 mg/kg）组、土鳖虫（3 g/kg）组和LL8高、低剂量（50、25 mg/kg）组，采用高脂饲料诱导建立高脂血症大鼠模型，各给药组ig相应药物，1次/d，连续3周，检测各组大鼠血浆中总胆固醇（total cholesterol，TC）、三酰甘油（triglycerides，TG）和低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）水平；检测各组大鼠肝脏组织中TC和TG水平；采用苏木素-伊红（HE）染色法观察各组大鼠肝组织病理变化。结果 高、低剂量LL8在SD大鼠体内的代谢趋势相似。与对照组比较，LL8组大鼠血浆中TG、TC和LDL-C水平显著降低（P<0.05），肝脏组织中TG、TC水平显著降低（P<0.05、0.01）。模型组大鼠肝脏组织内出现明显脂肪空泡与脂滴，各给药组大鼠肝脏脂肪变性明显改善。结论 LL8在SD大鼠体内半衰期较短，且能够抑制大鼠肝脏脂肪堆积，具有调血脂作用。

Objective To investigate the pharmacokinetics of bioactive peptide LL8 from Tubiechong (Steleophaga plancyi) on normal rats and effect of LL8 on hyperlipidemia rats. Methods Fluorescein isothiocyanate (FITC) was used for N-terminal labeling of LL8. SD rats were divided into high-, low-dose FITC-LL8 (10, 5 mg/kg) group, rats were im corresponding drugs, blood was taken at different time; EnSpire multi-label microplate inspection system, DAS 2.0 pharmacokinetic data processing software and partial least square calculation principle were used to calculate the pharmacokinetic changes of FITC-LL8 in SD rats. SD rats were randomly divided into control group, model group, simvastatin (200 mg/kg) group, S. plancyi (3 g/kg) group, high- and low-dose LL8 (50, 25 mg/kg) groups, high fat feed-induced rat models of hyperlipidemia were established. Rats in each administration group were ig corresponding drugs once a day for 3 weeks. Levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in plasma of each group were measured; Levels of TC and TG in liver tissues of rats in each group were detected; Hematoxylin-eosin (HE) staining method was used to observe the pathological changes of liver tissues of rats in each group. Results Metabolic trends of SD rats in high- and low-dose LL8 group were similar. Compared with control group, levels of TG, TC and LDL-C in plasma of rats in LL8 group were significantly reduced (P < 0.05), levels of TG and TC in liver tissue were significantly reduced (P < 0.05, 0.01). Obvious fat vacuoles and lipid droplets were appeared in liver tissues of rats in model group, and liver steatosis of rats in each administration group was significantly improved. Conclusion LL8 has a short half-life in SD rats, which can inhibit the accumulation of fat in liver of rats, and has the effect of regulating blood lipids.

R285.5;285.61

山东省青创人才引育团队——中药复杂体系作用模式解析创新研究团队项目（10073004）；烟台市校地融合发展中药大健康产业化平台项目（2019XDRHXMPT18）；滨州医学院高层次人才科研启动基金资助项目（2019KYQD05，2019KYQD06，BY2018KYQD11）；名贵中药资源可持续利用能力建设项目（2060302-1907-08）；山东省中药材及饮片标准研究项目（2020-004，2020-201，2020-202，2020-203，2020-204）